Allosteric regulation is a powerful tool utilized efficiently and elegantly in biological systems to control substrate binding and catalysis (Lim et al., Curr. Opin. Struct. Biol., 12:61 (2002); Kobe et al., Nature, 402:373 (1999)). Recently, advances have been made in the design of abiotic supramolecular structures that exhibit allosteric or pseudoallosteric behavior analogous to their biological counterparts. Sensors capable of signal amplification (Kovbasyuk et al., Chem. Rev., 104:3161 (2004); Saghatelian et al., J. Am. Chem. Soc., 125:344 (2003); Gianneschi et al., J. Am. Chem. Soc., 125:10508 (2003); Gianneschi et al., Angew. Chem. Int. Ed., 43:5503 (2004); Nabeshima et al., J. Am. Chem. Soc., 125:28 (2003); Nabeshima et al., Inorg. Chem., 32:1407 (1993); Reaendiz et al., Org. Lett., 6:651 (2004); Yoshizawa, et al., J. Am. Chem. Soc., 126:6846 (2004)) and asymmetric catalysts with activities and enantioselectivities that can be controlled with allosteric regulators have been designed (Gianneschi et al., J. Am. Chem. Soc., 125:10508 (2003); Gianneschi et al., Angew. Chem. Int. Ed., 43:5503 (2004)). Thus far, recognition of analytes induced by an allosteric regulator has not been demonstrated. This capability, however, would be a first step towards a system having recognition properties that could be selectively activated or deactivated using small molecule coordination chemistry at an allosteric regulatory site. Thus, the detection of an analyte of interest either through the allosteric effect of a second molecule on a coordination complex or through the allosteric effect that the analyte has on a coordination complex has not been achieved. Further, the use of these coordination complexes as catalysts with the ability to be activated or deactivated has not been demonstrated.
An analyte of interest can be detected by its ability to alter the coordination about a metal center of a coordination complex in a manner that affects the catalytic activity of the metal center. Alternatively, an analyte of interest can be detected through its ability to coordinate to the coordination complex only in one structural conformation of the coordination complex, wherein the structural conformation for binding the analyte is achieved through first binding an allosteric effector to a coordination complex. Further, the catalytic activity of a catalyst can be modulated by interaction between the catalyst and an allosteric effector.
The presence of the analyte can be detected by different methods, depending upon which of the two processes is in effect. In cases wherein the binding of the analyte activates the catalytic activity of the coordination complex, a product of the catalytic reaction can be detected. In cases wherein the binding of an allosteric effector causes a structural conformation change to the coordination complex, the analyte binds to the new structural conformation of the coordination complex and can be detected. This detection can be achieved through, for example, the addition of a fluorescent detection molecule that acts as a sensor for the binding of the analyte to the coordination complex.